Gliederung

The Metabolic Syndrome is the main risk factor for the development of cardiovascular disease, and abdominal obesity is the driving force for risk factor clustering. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB1) receptor reduces body weight in animals by central and peripheral actions, but the role of the peripheral endocannabinoid system for human obesity remains largely unknown. We measured circulating endocannabinoid concentrations and studied the expression of CB1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n=20) and abdominal obese (n=20) women with the metabolic syndrome, and following 5% weight loss (n=17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35% and 52% in obese compared to lean women, respectively (p<0.05). Adipose tissue mRNA levels were reduced by -34% for CB1 and by -59% for FAAH in obese subjects (p<0.05). A negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB1 or FAAH expression were not affected by 5% weight loss. Expression of CB1 and FAAH was markedly increased in mature human adipocytes compared to preadipocytes and was found in several other human tissues related to glucose and lipid metabolism. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human abdominal obesity.